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10/4/18
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ACLS & Beyond
Christa Creech, Pharm.D.PGY-2 Emergency Medicine Pharmacy Resident
October 7th, 2018
ObjectivesList recent changes to ACLS guidelines applicable to pharmacists
Recognize reversible causes of cardiac arrest and be familiar with their treatments
Recommend adjunctive therapies for refractory cases of cardiac arrest
ACLS = Advanced cardiovascular life support
Outline – ACLS & Beyond
Summary of recent updates to ACLS
guidelines
ACLS algorithm review• Shockable rhythms• Non-shockable rhythms• Reversible causes of
cardiac arrest
Other drugs you may encounter during
cardiac arrest circumstances
Access & routes of administration Procedural support
ACLS = Advanced cardiovascular life support
Summary of Guideline Updates
2010 à 2015
Next update in 2020
Post-cardiac arrest careComatose patients should be cooled for 12-24
hoursComatose patients should be cooled for > 24
hours
Extracorporeal CPRInsufficient information to recommend routine
use of extracorporeal CPRExtracorporeal CPR may be considered instead
of regular CPR for reversible cardiac arrest
VasopressinVasopressin may replace the first or second
dose of epinephrineVasopressin plus epinephrine provides no advantage as a substitute for epinephrine
Depth & FrequencyAt least 2 inches & at least 100 compressions
per minute2-2.5 inches in adults & no less than 100 but no
more than 120 compressions per minute
Sequence
Airway, breathing, circulation Circulation, airway, breathing
2010 2015
Link. Circulation. 2015;132(18 Suppl 2):S444-64.Morrison. Circulation. 2010;122(18 Suppl 3):S665-75.
Circulation - Airway - Breathing•2-2.5 inches depth for adults•100 - 120 compressions per minuteCPR• Avoid excessive ventilation• 30:2 compression ventilation ratioO2
• Attach monitor• DefibrillatorMonitoring
•Peripheral IV, central IV, IO, ETAccessMarsch. Swiss Med Wkly. 2013;143:w13856.
Link. Circulation. 2015;132(18 Suppl 2):S444-64.IV = intravenousCPR = Cardiopulmonary resuscitation
IO = intraosseousET = endotracheal
Assess Rhythm for Shockability
VF &
pVT
Asystole&
PEA
Link. Circulation. 2015;132(18 Suppl 2):S444-64.VF = Ventricular fibrillation pVT = Pulseless ventricular fibrillation PEA = Pulseless electrical activity
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Electricity Versus Pharmacotherapy“Some antiarrhythmic drugs have been associated with increased rates of ROSC and hospital admission, but
none have yet been proven to increase long-term survival or survival with good neurological outcome.
Thus, establishing vascular access to enable drug administration should not compromise the quality of
CPR or timely defibrillation, which are known to improve survival.”
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Shockable Rhythm Algorithm
Shockable Rhythms
VF/pVT
Shock
CPR x 2 minutes
IV/IO access
Link. Circulation. 2015;132(18 Suppl 2):S444-64.IO = intraosseousVF = Ventricular fibrillation pVT = Pulseless ventricular fibrillation
IV = intravenousCPR = Cardiopulmonary resuscitation
VF/pVT s/p 1 shock & 2 min of CPR
Reassess rhythm
Shock
CPR x 2 minEpinephrine 1mg every 3-
5 minutes
Consider advanced
airway
PEA/Asystole ROSC
Not Shockable Shockable
Link. Circulation. 2015;132(18 Suppl 2):S444-64.PEA = Pulseless electrical activityROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation
VF/pVT s/p 2 shocks & 4 min of CPR
Reassess rhythm
Shock
CPR x 2 min AmiodaroneTreat
reversible causes
PEA/Asystole ROSC
Not ShockableShockable
Link. Circulation. 2015;132(18 Suppl 2):S444-64.PEA = Pulseless electrical activityROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation
Algorithm DrugsDrug Initial Dose Drip MOA
Epinephrine
1 mg IV/IO pushEvery 3-5 minET: 2-2.5 mg every 3-5 min
1-30 mcg/min
(4 mg/250ml)
Stimulates beta-1, beta-2 and alpha-1 adrenergic receptors to produce an increase in cardiac contractility, heart rate, systemic vascular resistance and blood pressure
Amiodarone300 mg IV/IO x 1, may repeat 10 min 150 mg
1 mg/min for 6 h à0.5 mg/min x 18 h900mg in 500ml of D5W (1.8 mg/ml)
Iinhibits adrenergic stimulation, prolongs the action potential, and prolongs the refractory period in myocardial tissue
Link. Circulation. 2015;132(18 Suppl 2):S444-64.IV = IntravenousIO = intraosseous D5W = 5% dextrose in water
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What’s in your crash cart?
Epinephrine
PARAMEDIC2 Trial• RCT, 8014 patients, out-of-hospital arrest• Epinephrine à increased 30-day survival• No difference in rate of favorable
neurologic outcomes
Perkins. N Engl J Med. 2018;RCT = Randomized controlled trial
Epinephrine
• Prospective, non-randomized observational propensity analysis
• Included data from 417188 out-of-hospital cardiac arrests
• Epinephrine associated with increased chance of ROSC before hospital arrival
• Reduced chance of survival and good functional outcomes 1 month after event
• Double-blind RCT • 534 out-of-hospital cardiac arrests• Epinephrine vs. placebo
• Epinephrine associated with increased chance of ROSC before hospital arrival
• No significant improvement in survival to hospital discharge
Hagihara. JAMA. 2012;307(11):1161-8. Jacobs. Resuscitation. 2011;82(9):1138-43.RCT = Randomized controlled trial
ROSC= Return of spontaneous circulation
Cumulative Dose of EpinephrineDoes the cumulative
epinephrine dose impact neurologic outcome after
cardiac arrest?
3 retrospective studies show association of
higher cumulative doses and worse neurologic
outcome
Lack of consistency regarding how much
epinephrine is too muchMultiple existing
confounders
Difficult to draw conclusions from the
existing data
Rivers. Chest. 1994;106(5):1499-507.Behringer. Ann Intern Med. 1998;129(6):450-6.
Arrich. Resuscitation. 2012;83(3):333-7.Laureys. Nat Rev Neurosci. 2005;6(11):899-909.
Cumulative Dose of Epinephrine
Are we giving too much epinephrine?
Evidence is not currently strong enough to support implementation of a dose threshold
Rivers. Chest. 1994;106(5):1499-507.Behringer. Ann Intern Med. 1998;129(6):450-6.Arrich. Resuscitation. 2012;83(3):333-7.
Dose
Cumulative Dose of Epinephrine
Consider giving guideline recommended dose every 5 minutes
Rivers. Chest. 1994;106(5):1499-507.Behringer. Ann Intern Med. 1998;129(6):450-6.Arrich. Resuscitation. 2012;83(3):333-7.
Dose
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Non-ShockableRhythm Algorithm
Non-Shockable Rhythms
Asystole/PEA
CPR x 2 min IV/IO accessConsider advanced
airway
Link. Circulation. 2015;132(18 Suppl 2):S444-64.PEA = Pulseless electrical activityCPR = Cardiopulmonary resuscitation
IV = intravenousIO = intraosseous
Non-Shockable Rhythms
Reassess rhythm
Asystole/PEA
CPR x 2 minTreat
Reversible causes
VF/pVT ROSC
Link. Circulation. 2015;132(18 Suppl 2):S444-64.CPR = Cardiopulmonary resuscitationROSC= Return of spontaneous circulation
VF = Ventricular fibrillation pVT = Pulseless ventricular fibrillation PEA = Pulseless electrical activity
Reversible Causes
H’s • Hypoxia, hypovolemia, hydrogen ion,
hypo-/hyperkalemia, and hypothermia
T’s • Tension pneumothorax, tamponade, toxins,
thrombosis (pulmonary), and thrombosis (coronary)
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
H’s
Hypovolemia Hypoxia Hydrogen ion (acidosis)
Hypo-/hyperkalemia Hypothermia Hypoglycemia
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Hypoxia
O2 Albuterol RSI
RSI = Rapid sequence intubation
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H’s
Hypovolemia Hypoxia Hydrogen ion (acidosis)
Hypo-/hyperkalemia Hypothermia Hypoglycemia
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Hypovolemia
Look for obvious fluid loss
• Blood• Dehydration• Severe burns• N/V/D
Obtain IV access
• Most important intervention
• Can also obtain IO if equipmentavailable
Fluidchallenge
• At least 2L of isotonic crystalloid
• +/- pressure bag
N/V/D = Nausea/vomiting/diarrheaIV = intravenousIO = intraosseous
H’s
Hypovolemia Hypoxia Hydrogen ion (acidosis)
Hypo-/hyperkalemia Hypothermia Hypoglycemia
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Hydrogen Ion (Acidosis)
Respiratoryacidosis
10 breaths per minute
Metabolic acidosis
Sodium bicarbonate 50
mEq/50 mL
Sodium Bicarbonate • Prolonged CPR can result in profound acidosis• Sodium bicarbonate thought to increase pH to
allow better activity of catecholamines in alkaline environment
Why is it given?
• Can result in paradoxical acidosis• Will not resolve underlying cause of acidosis
Rapid Push
• Tricyclic antidepressant overdose• Aspirin overdose• Wide QRS
Best used for
H’s
Hypovolemia Hypoxia Hydrogen ion (acidosis)
Hypo-/hyperkalemia Hypothermia Hypoglycemia
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
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Hypokalemia
- Excessive N/V/D & excessive use of diuretics
- Blunted T waves, prominent U waves, and possible wide QRS on EKG
- Treat with controlled infusion of KCl
- 2 mEq per minute for 10 minutes
- Followed by 10 mEq over 5-10 minutes
K+
EKG = ElectrocardiographyKCl = Potassium chlorideN/V/D = Nausea/vomiting/diarrhea Truhlář . Resuscitation. 2015;95:148-201.
Hyperkalemia
Calcium chloride or gluconate-Stabilizes
cardiac membranes
Beta 2 agonists &
Bicarbonate-Shift K+ into
cells
Insulin & Glucose
-Shifts K+ into cells
-Prevent hypoglycemia
Kayexalate-Binds K in
gut, excretion through feces
Dialysis or diuretics
-If refractory to all other
options
C IG K DIB
T’s
Tension Pneumothorax
Tamponade (cardiac) Toxins
Thrombosis (pulmonary)
Thrombosis (coronary) Trauma
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Tension Pneumothorax
Tracheal deviation, unequal breath sounds, pulseless, narrow QRS, bradycardia, JVD
Needle decompression
Chest tube
JVD = Jugular vein distention
T’s
Tension Pneumothorax
Tamponade (cardiac) Toxins
Thrombosis (pulmonary)
Thrombosis (coronary) Trauma
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Tamponade (Cardiac)
Signs
EKG
Treatment
• JVD• Muffled heart
sounds
• Tachycardia• Narrow QRS
• Ultrasound• Pericardiocentesis
JVD = Jugular vein distentionEKG = electrocardiography
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T’s
Tension Pneumothorax
Tamponade (cardiac) Toxins
Thrombosis (pulmonary)
Thrombosis (coronary) Trauma
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Toxins
Opioids
Pinpoint pupils, respiratory depression
Naloxone IN/IV
QT prolonging drugs
QTC >500 ms
Magnesium Sulfate 2g IV
bolus
Benzodiazepines
CNS depression
Flumazenil 0.2 mg IV over 30s
CNS = Central nervous systemIN/IV = Intranasal / intravenous
Additional Toxins
Beta Blockers
Bradycardia, hypotension, hypoglycemia
Glucagon, insulin, atropine,
catecholamines, calcium, pacing
Calcium Channel Blockers
Hypotension, bradycardia, acidosis,
hypoglycemia
Calcium chloride, insulin, glucagon, catecholamines, methylene blue
Serotonergic Drugs
Tremor, hyperreflexia, muscle rigidity,
hyperthermia, AMS
Supportive care, benzodiazepines cyproheptadine
AMS = Altered mental status
T’s
Tension Pneumothorax
Tamponade (cardiac) Toxins
Thrombosis (pulmonary)
Thrombosis (coronary) Trauma
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Thrombosis (Pulmonary)
Thrombolytic TherapyHypotensionTachycardia
Narrow QRS
Shortness of breath
Respiratory Support O2 >90%
IV Fluids 500mL-1L
NS
Wells score & risk of bleeding
IV = intravenousNS = normal saline
Thrombolytic Therapy for Pulmonary EmboliCitation Study Design Drug Dose
Kurkciyanet al.
Retrospective cohort Alteplase 100 mg (either two 50 mg boluses OR 15 mg
bolus followed by 85 mg over 90 min)
Ruiz-Bailenet al.
Case series (6 pts) Alteplase 50 mg bolus, repeat 50 mg in 30 min
Janata et al.
Retrospective cohort
Alteplase 0.6-1.0 mg/kg bolus (up to 100 mg)
Sharifi et al. Case series (23 pts)
Alteplase 50 mg bolus
Sharifi . Am J Emerg Med. 2016;34(10):1963-1967.Kürkciyan. Arch Intern Med. 2000;160(10):1529-1535.
Janata. Resuscitation. 2003;57(1):49-55.Ruiz-Bailén. Resuscitation. 2001;51(1):97-101.
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Thrombolytic Therapy for Pulmonary Emboli
• Retrospective cohort study (n = 3768)• Adult critically ill patients with acute PE treated with
systemic alteplase therapy• 50 mg (n = 699) vs. 100 mg (n = 3069)
• Patients that received 50 mg (half-dose) alteplase• Similar mortality rates • Similar rates of major bleeding
• Half-dose may provide similar efficacy & improved safety
PE = pulmonary embolism Kiser. Crit Care Med. 2018;46(10):1617-1625.
T’s
Tension Pneumothorax
Tamponade (cardiac) Toxins
Thrombosis (pulmonary)
Thrombosis (coronary) Trauma
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
Acute MI à Arrest Citation Study Design Drug Dose
Ledereret al.
Retrospective cohort Alteplase 100 mg (15 mg followed by 85 mg over 90 min)
Ruiz-Bailenet al.
Retrospective cohort Alteplase 100 mg (either two 50 mg boluses OR
15 mg bolus followed by 85 mg over 90 min)
Schreiber et al.
Retrospective cohort
Alteplase 100 mg (15 mg followed by 85 mg over 90 min)
Kurkciyanet al.
Retrospective cohort
Alteplase 100 mg (15 mg followed by 85 mg over 90 min)
MI = Myocardial infarctionLederer . Resuscitation. 2001;50(1):71-76.
Ruiz-Bailén. Intensive Care Med. 2001;27(6):1050-1057.Schreiber. Resuscitation. 2002;52(1):63-69.Kurkciyan. J Intern Med. 2003;253(2):128-135.
Thrombosis (Coronary)
Morphine• 2-4 mg IV every 5-
15 minutes• Reserve use for
patients with an unacceptable level of pain
• CRUSADE - higher adjusted risk of death
Oxygen• If <90%• No difference in
mortality• AVOID – no reduction
in size of infarction• Shown to cause
direct vasoconstriction ofcoronaries
Nitroglycerin• Up to 3 sublingual
NTG tablets (1 every 5 minutes)
• Avoid if hypotensive, or if taken a PDEiwithin past 24 hours
Aspirin•324 mg chewed• Significant reduction in 5 week vascular mortality• Reduction in non-fatal re-infarction•No increase in risk of major bleeding
Meine . Am Heart J. 2005;149(6):1043-9.Stub. Circulation. 2015;131(24):2143-50.
Thrombolysis Takeaways (PE & MI)
The dose of alteplase for cardiac arrest is between 50
and 100 mg given as a bolus +/-an infusion
Continued CPR is not an absolute contraindication for
fibrinolysis
Some studies suggest allowing 15 minutes of
CPR for the drug to work
Anticoagulants (primarily heparin) were used in most studies with the
fibrinolytic
PE = pulmonary embolismMI = myocardial infarction CPR = cardiopulmonary resuscitation
T’s
Tension Pneumothorax
Tamponade (cardiac) Toxins
Thrombosis (pulmonary)
Thrombosis (coronary) Trauma
Link. Circulation. 2015;132(18 Suppl 2):S444-64.
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Trauma
Advanced Trauma Life Support
Target audience: surgeons in hospitals & trauma centers
Removed from H’s & T’s but still important be aware of
Traumatic arrests typically due to hypovolemia
Copyright © 1996-2018 by the American College of Surgeons, Chicago, IL 60611-3295
Other DrugsFOR OTHER CIRCUMSTANCES OUTSIDE OF THE H’S & T’S
Other DrugsMagnesium sulfate
Recommended for torsades de pointes associated with a long QT interval
Magnesium sulfate 1-2 g diluted in 10 mL D5W IV/IO
Vasopressin
Previously recommended as a substitute for the first or second dose of epinephrineThought to sensitize to catecholamines and work at a lower pH than other pressors
Recently removed recommendation from new guidelines
IV = intravenousIO = intraosseous D5W =5% dextrose in water
Vasopressin No Longer Recommended
• Small RCT (n = 44)• Epinephrine & vasopressin vs. epinephrine
+ vasopressin + nitroglycerin vs. epinephrine alone
• The combination(s) did not achieve a higher diastolic blood pressure than epinephrine alone
• Larger RCT (n = 727)• Vasopressin vs. epinephrine
• No difference in rate of survival at discharge• Vasopressin not worse than epinephrine
Ducros. J Emerg Med. 2011;41(5):453-9.Ong. Resuscitation. 2012;83(8):953-60.RCT = Randomized controlled trial
Esmolol
For “refractory” ventricular fibrillation
Excessive catecholamines thought to have harmful effects on myocardium via β-1 receptor agonism• Increased myocardial oxygen requirements, worsening ischemic injury,
lowering of VF threshold, and worse post-resuscitation myocardial function
Antagonism of β-1 receptors theoretically mitigate the above potentially harmful effects of epinephrine while preserving beneficial alpha-receptor actions
VF = Ventricular fibrillation Evans. Emerg Med J. 2016;33(5):367-8.
Esmolol
• Case series • 6 RVF patients received esmolol• 19 RVF control patients
• Overall 4/6 patients achieved sustained ROSC following a 500 mcg bolus & infusion of esmolol
• The other 2 patients that received esmolol achieved temporary ROSC• Subsequently re-arrested & expired
Driver. Resuscitation. 2014;85(10):1337-41..
RVF = refractory ventricular fibrillationROSC = return of spontaneous circulation
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Esmolol
Conclusions – esmolol vs. standard of care
• Esmolol increased temporary ROSC (67% vs. 42%)• Esmolol increased sustained ROSC (67% vs. 32%)
• Esmolol increased survival to hospital discharge (50% vs. 16%)• Esmolol increased survival to discharge with a favorable neurological
outcome (50% vs. 11%)
Driver. Resuscitation. 2014;85(10):1337-41..
ROSC = return of spontaneous circulation
Esmolol
• Pre- & Post-cohort study following implementation of esmolol for RVF in out-of-hospital cardiac arrest
• Esmolol bolus of 500 mcg à continuous infusion• Esmolol (n = 16) non-esmolol (n = 25)
• Esmolol group demonstrated a higher rate of temporary ROSC, sustained ROSC, & survival to the intensive care unit
RVF = refractory ventricular fibrillationROSC = return of spontaneous circulation Lee. Resuscitation. 2016;107:150-5.
.
Access & Routes of Administration
Intraosseous
Proximal humerus
Proximal tibia
Distal tibia
• All medications (including blood products) may be safely administered through the IO line
• Onset & peak drug levels are comparable to IV• Important to be mindful of compatibility
IV = intravenousIO = intraosseous
MC-002864
IO Infusion Pain Management
LidocaineInitialdose120seconds
Dwell60seconds RapidFlush
Lidocaine½initialdose60seconds
2%lidocaine(preservative-freeandepinephrine-free)
Adult:Typically40mgInfant/Child:Typically0.5mg/kg(NOTtoexceed40mg)
≥4minutestotaltime
Epinephrine• May be asked for during a thoracotomy in traumatic arrest • Dosing is the same as in ACLS
• à 1 mg every 3-5 minutes • Both concentrations acceptable
• 1:10,000 (1 mg/10 mL)• 1:1,000 (1 mg/mL)
• Needle• 18-22 gauge• 1.5 inches
• Injection• Directly into chamber of left ventricle as a rapid push
Intracardiac
ACLS = Advanced cardiovascular life support
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• Stop chest compressions, spray drug down the tube• Immediately give 5 manual ventilations to create
aerosol Drug Delivery
• Can affect the rate of absorption of the drug• Use saline rather than distilled waterDiluents
• The ideal volume for ET drug delivery has not been determined
• ~10 mL to avoid insufficient absorption or hypoxia Volume
• Drugs given the ET route should be about 2-1.5 times the recommended doseDose
• The duration of actions of drugs given ET is prolonged (depot effect) Duration
Endotracheal Tube
idocaine 2-3 mg/kgpinephrine 2-2.5 mgtropine 1-2 mgaloxone 0.8-5 mg
Ward. Am J Emerg Med. 1983;1:71-82.ET = endotracheal tube
Procedural Support
Pharmacologic Considerations During ECMO
Anticoagulation
Bolus of unfractionated heparin 50-100 units/kg (max ~ 5000 units)
Data does not support the use of anti-thrombin III
May be monitored via anti-Xa, ACT, or PTT
Sedation & Analgesia
Higher doses typically required
Cannulation location can influence goal level of sedation
Always use minimum necessary to avoid delirium if possible
Paralytics
May be needed if patient is centrally cannulated
Long acting paralytic pushes
Paralytic infusion
ACT = Activated clotting timePTT = Partial thromboplastin time
ELSO. Version 1.4 . 2017. Byrnes. ASAIO J. 2014;60(1):57-62.
Summary• Most pharmacy relevant update is the removal of vasopressin from the
algorithm
ACLS guidelines
• H’s: hypovolemia, hypoxia, hydrogen ion (acidosis), hyper-/hypokalemia, hypothermia, & hypoglycemia
• T’s: toxins, tamponade (cardiac), tension pneumothorax, thrombosis (coronary & pulmonary), & trauma
Reversible causes of cardiac arrest
• May be treated with esmolol
Refractory ventricular fibrillation
ACLS = Advanced cardiovascular life support
ACLS & Beyond
Christa Creech, Pharm.D.PGY-2 Emergency Medicine Pharmacy Resident
October 7th, 2018